Of the diagnostic methods available to veterinarians, the clinical
chemistry test has developed into a valuable aid for localizing pathologic
conditions. This test is actually a collection of specially selected individual
tests. With just a small amount of whole blood or serum, many body
systems can be analyzed. Some of the more common screenings give
information about the function of the kidneys, liver, and pancreas and
about muscle and bone disease. There are many blood chemistry tests
available to doctors. This paper covers the some of the more common
Blood urea nitrogen (BUN) is an end-product of protein metabolism. Like
most of the other molecules in the body, amino acids are constantly
renewed. In the course of this turnover, they may undergo deamination,
the removal of the amino group. Deamination, which takes place
principally in the liver, results in the formation of ammonia. In the liver,
the ammonia is quickly converted to urea, which is relatively nontoxic,
and is then released into the bloodstream. In the blood, it is readily
removed through the kidneys and excreted in the urine. Any disease or
condition that reduces glomerular filtration or increases protein
catabolism results in elevated BUN levels.
Creatinine is another indicator of kidney function. Creatinine is a waste
product derived from creatine. It is freely filtered by the glomerulus and
blood levels are useful for estimating glomerular filtration rate. Muscle
tissue contains phosphocreatinine which is converted to creatinine by a
nonenzymatic process. This spontaneous degradation occurs at a rather
consistent rate (Merck, 1991).
Causes of increases of both BUN and creatinine can be divided into three
major categories: prerenal, renal, and postrenal. Prerenal causes include
heart disease, hypoadrenocorticism and shock. Postrenal causes include
urethral obstruction or lacerations of the ureter, bladder, or urethra. True
renal disease from glomerular, tubular, or interstitial dysfunction raises
BUN and creatinine levels when over 70% of the nephrons become
nonfunctional (Sodikoff, 1995).
Glucose is a primary energy source for living organisms. The glucose
level in blood is normally controlled to within narrow limits. Inadequate
or excessive amounts of glucose or the inability to metabolize glucose
can affect nearly every system in the body. Low blood glucose levels
(hypoglycemia) may be caused by pancreatic tumors (over-production of
insulin), starvation, hypoadrenocorticism, hypopituitarism, and severe
exertion. Elevated blood glucose levels (hyperglycemia) can occur in
diabetes mellitus, hyperthyroidism, hyperadrenocorticism,
hyperpituitarism, anoxia (because of the instability of liver glycogen in
oxygen deficiency), certain physiologic conditions (exposure to cold,
digestion) and pancreatic necrosis (because the pancreas produces insulin
which controls blood glucose levels).
Diabetes mellitus is caused by a deficiency in the secretion
or action of insulin. During periods of low blood glucose, glucagon
stimulates the breakdown of liver glycogen and inhibits glucose
breakdown by glycolysis in the liver and stimulates glucose synthesis by
gluconeogenesis. This increases blood glucose. When glucose enters the
bloodstream from the intestine after a carbohydrate-rich meal, the
resulting increase in blood glucose causes increased insulin secretion and
decreased glucagon secretion. Insulin stimulates glucose uptake by
muscle tissue where glucose is converted to glucose-6-phosphate. Insulin
also activates glycogen synthase so that much of the
glucose-6-phosphate is converted to glycogen. It also stimulates the
storage of excess fuels as fat (Lehninger, 1993).
With insufficient insulin, glucose is not used by the tissues and
accumulates in the blood. The accumulated glucose then spills into the
urine. Additional amounts of water are retained in urine because of the
accumulation of glucose and polyuria (excessive urination) results. In
order to prevent dehydration, more water than normal is consumed
(polydipsia). In the absence of insulin, fatty acids released form adipose
tissue are converted to ketone bodies (acetoacetic acid, B-hydroxybutyric
acid, and acetone). Although ketone bodies can be used a energy
sources, insulin deficiency impairs the ability of tissues to use ketone
bodies, which accumulate in the blood. Because they are acids, ketones
may exhaust the ability of the body to maintain normal pH. Ketones are
excreted by the kidneys, drawing water with them into the urine. Ketones
are also negatively charged and draw positively charged ions (sodium,
potassium, calcium) with them into urine. Some other results of diabetes
mellitus are cataracts (because of abnormal glucose metabolism in the
lens which results in the accumulation of water), abnormal neutrophil
function (resulting in greater susceptibility to infection), and an enlarged
liver (due to fat accumulation) (Fraser, 1991).
Bilirubin is a bile pigment derived from the breakdown of heme by the
reticuloendothelial system. The reticuloendothelial system filters out and
destroys spent red blood cells yielding a free iron molecule and
ultimately, bilirubin. Bilirubin binds to serum albumin, which restricts it
from urinary excretion, and is transported to the liver. In the liver,
bilirubin is changed into bilirubin diglucuronide, which is sufficiently
water soluble to be secreted with other components of bile into the small
intestine. Impaired liver function or blocked bile secretion causes
bilirubin to leak into the blood, resulting in a yellowing of the skin and
eyeballs (jaundice). Determination of bilirubin concentration in the blood
is useful in diagnosing liver disease (Lehninger, 1993). Increased
bilirubin can also be caused by hemolysis, bile duct obstruction, fever,
and starvation (Bistner, 1995).
Two important serum lipids are cholesterol and triglycerides. Cholesterol
is a precursor to bile salts and steroid hormones. The principle bile salts,
taurocholic acid and glycocholic acid, are important in the digestion of
food and the solubilization of ingested fats. The desmolase reaction
converts cholesterol, in mitochondria, to pregnenolone which is
transported to the endoplasmic reticulum and converted to progesterone.
This is the precursor to all other steroid hormones (Garrett, 1995).
Triglycerides are the main form in which lipids are stored and are the
predominant type of dietary lipid. They are stored in specialized cells
called adipocytes (fat cells) under the skin, in the abdominal cavity, and
in the mammary glands. As stored fuels, triglycerides have an advantage
over polysaccharides because they are unhydrated and lack the extra
water weight of polysaccharides. Also, because the carbon atoms are
more reduced than those of sugars, oxidation of triglycerides yields more
than twice as much energy, gram for gram, as that of carbohydrates
Hyperlipidemia refers to an abnormally high concentration of triglyceride
and/or cholesterol in the blood. Primary hyperlipidemia is an inherited
disorder of lipid metabolism. Secondary hyperlipidemias are usually
associated with pancreatitis, diabetes mellitus, hypothyroidism, protein
losing glomerulonephropathies, glucocorticosteroid administration, and a
variety of liver abnormalities. Hypolipidemia is almost always a result of
malnutrition (Barrie, 1995).
Alkaline phosphatase is present in high concentration in bone and liver.
Bone remodeling (disease or repair) results in moderate elevations of
serum alkaline phosphatase levels, and cholestasis (stagnation of bile
flow) and bile duct obstruction result in dramatically increased serum
alkaline phosphatase levels. The obstruction is usually intrahepatic,
associated with swelling of hepatocytes and bile stasis. Elevated serum
alkaline phosphatase and bilirubin levels suggest bile duct obstruction.
Elevated serum alkaline phosphatase and normal bilirubin levels suggest
hepatic congestion or swelling. Elevations also occur in rapidly growing
young animals and in conditions causing bone formation (Bistner, 1995).
Aspartate aminotransferase (AST) is an enzyme normally found in the
mitochondria of liver, heart, and skeletal muscle cells. In the event of
heart or liver damage, AST leaks into the blood stream and
concentrations become elevated (Bistner, 1995). AST, along with alkaline
phosphatase, are used to differentiate between liver and muscle damage
Alanine aminotransferase (ALT) is considered a liver-specific enzyme,
although small amounts are present in the heart. ALT is generally located
in the cytosol. Liver disease results in the releasing of the enzyme into
the serum. Measurements of this enzyme are used in the diagnosis of
certain types of liver diseases such as viral hepatitis and hepatic necrosis,
and heart diseases. The ALT level remains elevated for more than a week
after hepatic injury (Sodikoff, 1995).
Fibrinogen, albumin, and globulins constitute the major proteins of the
blood plasma. Fibrinogen, which makes up about 0.3 percent of the total
protein volume, is a soluble protein involved in the clotting process. The
formation of blood clots is the result of a series of zymogen activations.
Factors released by injured tissues or abnormal surfaces caused by injury
initiate the clotting process. To create the clot, thrombin removes
negatively charged peptides from fibrinogen, converting it to fibrin. The
fibrin monomer has a different surface charge distribution than
fibrinogen. These monomers readily aggregates into ordered fibrous
arrays. Platelets and plasma globulins release a fibrin-stabilizing factor
which creates cross-links in the fibrin net to stabilize the clot. The clot
binds the wound until new tissue can be built (Garrett, 1995).
The alpha-, beta-, and gamma-globulins compose the globulins.
Alpha-globulins transport lipids, hormones, and vitamins. Also included
is a glycoprotein, ceruloplasmin, which carries copper and
haptoglobulins, which bind hemoglobin. Iron transport is related to
beta-globulins. The glycoprotein that binds the iron is transferrin
(Lehninger, 1993). Gamma-globulins (immunoglobulins) are associated
with antibody formation. There are five different classes of
immunoglobulins. IgG is the major circulating antibody. It gives immune
protection within the body and is small enough to cross the placenta,
giving newborns temporary protection against infection. IgM also gives
protection within the body but is too large to cross the placenta. IgA is
normally found in mucous membranes, saliva, and milk. It provides
external protection. IgD is thought to function during the development
and maturation of the immune response. IgE makes of the smallest
fraction of the immunoglobulins. It is responsible for allergic and
Altered levels of alpha- and beta- globulins are rare, but immunoglobulin
levels change in various conditions. Serum immunoglobulin levels can
increase with viral or bacterial infection, parasitism, lymphosarcoma, and
liver disease. Levels are decreased in immunodeficiency.
Albumin is a serum protein that affects osmotic pressure, binds many
drugs, and transports fatty acids. Albumin is produced in the liver and is
the most prevalent serum protein, making up 40 to 60 percent of the
total protein. Serum albumin levels are decreased (hypoalbuminemia) by
starvation, parasitism, chronic liver disease, and acute glomerulonephritis
(Sodikoff, 1995). Albumin is a weak acid and hypoalbuminemia will tend
to cause nonrespiratory alkalosis (de Morais, 1995). Serum albumin
levels are often elevated in shock or severe dehydration.
Creatine Kinase (CK) is an enzyme that is most abundant in skeletal
muscle, heart muscle, and nervous tissue. CK splits creatine phosphate in
the presence of adenosine diphosphate (ADP) to yield creatine and
adenosine triphosphate (ATP). During periods of active muscular
contraction and glycolysis, this reaction proceeds predominantly in the
direction of ATP synthesis. During recovery from exertion, CK is used to
resynthesize creatine phosphate from creatine at the expense of ATP.
After a heart attack, CK is the first enzyme to appear in the blood
(Lehninger, 1993). CK values become elevated from muscle damage
(from trauma), infarction, muscular dystrophies, or inflammation.
Elevated CK values can also be seen following intramuscular injections of
irritating substances. Muscle diseases may be associated with direct
damage to muscle fibers or neurogenic diseases that result in secondary
damage to muscle fibers. Greatly increased CK values are usually
associated with heart muscle disease because of the large number of
mitochondria in heart muscle cells (Bistner, 1995).
When active muscle tissue cannot be supplied with sufficient oxygen, it
becomes anaerobic and produces pyruvate from glucose by glycolysis.
Lactate dehydrogenase (LDH) catalyzes the regeneration of NAD+ from
NADH so glycolysis can continue. The lactate produced is released into
the blood. Heart tissue is aerobic and uses lactate as a fuel, converting it
to pyruvate via LDH and using the pyruvate to fuel the citric acid cycle to
obtain energy (Lehninger, 1993). Because of the ubiquitous origins of
LDH, the total serum level is not reliable for diagnosis; but in normal
serum, there are five isoenzymes of LDH which give more specific
information. These isoenzymes can help differentiate between increases
in LDH due to liver, muscle, kidney, or heart damage or hemolysis
Calcium is involved in many processes of the body, including
neuromuscular excitability, muscle contraction, enzyme activity, hormone
release, and blood coagulation. Calcium is also an important ion in that it
affects the permeability of the nerve cell membrane to sodium. Without
sufficient calcium, muscle spasms can occur due to erratic, spontaneous
The majority of the calcium in the body is found in bone as phosphate
and carbonate. In blood, calcium is available in two forms. The
nondiffusible form is bound to protein (mainly albumin) and makes up
about 45 percent of the measurable calcium. This bound form is inactive.
The ionized forms of calcium are biologically active. If the circulating
level falls, the bones are used as a source of calcium.
Primary control of blood calcium is dependent on parathyroid hormone,
calcitonin, and the presence of vitamin D. Parathyroid hormone
maintains blood calcium level by increasing its absorption in the
intestines from food and reducing its excretion by the kidneys.
Parathyroid hormone also stimulates the release of calcium into the
blood stream from the bones. Hyperparathyroidism, caused by tumors of
the parathyroid, causes the bones to lose too much calcium and become
soft and fragile. Calcitonin produces a hypocalcemic effect by inhibiting
the effect of parathyroid hormone and preventing calcium from leaving
bones. Vitamin D stimulates calcium and phosphate absorption in the
small intestine and increases calcium and phosphate utilization from
bone. Hypercalcemia may be caused by abnormal calcium/phosphorus
ratio, hyperparathyroidism, hypervitaminosis D, and hyperproteinemia.
Hypocalcemia may be caused by hypoproteinemia, renal failure, or
pancreatitis (Bistner, 1995).
Because approximately 98 percent of the total body potassium is found at
the intracellular level, potassium is the major intracellular cation. This
cation is filtered by the glomeruli in the kidneys and nearly completely
reabsorbed by the proximal tubules. It is then excreted by the distal
tubules. There is no renal threshold for potassium and it continues to be
excreted in the urine even in low potassium states. Therefore, the body
has no mechanism to prevent excessive loss of potassium
Potassium plays a critical role in maintaining the normal cellular and
muscular function. Any imbalance of the body’s potassium level,
increased or decreased, may result in neuromuscular dysfunction,
especially in the heart muscle. Serious, and sometimes fatal, arrythmias
may develop. A low serum potassium level, hypokalemia, occurs with
major fluid loss in gastrointestinal disorders (i.e., vomiting, diarrhea),
renal disease, diuretic therapy, diabetes mellitus, or mineralocorticoid
dysfunction (i.e., Cushing’s disease). An increased serum potassium
level, hyperkalemia, occurs most often in urinary obstruction, anuria, or
acute renal disease (Bistner, 1995).
Sodium and its related anions (i.e., chloride and bicarbonate) are
primarily responsible for the osmotic attraction and retention of water in
the extracellular fluid compartments. The endothelial membrane is freely
permeable to these small electrolytes. Sodium is the most abundant
extracellular cation, however, very little is present intracellularly. The
main functions of sodium in the body include maintenance of membrane
potentials and initiation of action potentials in excitable membranes. The
sodium concentration also largely determines the extracellular osmolarity
and volume. The differential concentration of sodium is the principal
force for the movement of water across cellular membranes. In addition,
sodium is involved in the absorption of glucose and some amino acids
from the gastrointestinal tract (Lehninger, 1993). Sodium is ingested
with food and water, and is lost from the body in urine, feces, and sweat.
Most sodium secreted into the GI tract is reabsorbed. The excretion of
sodium is regulated by the renin-angiotensin-aldosterone system
Decreased serum sodium levels, hyponatremia, can be seen in adrenal
insufficiency, inadequate sodium intake, renal insufficiency, vomiting or
diarrhea, and uncontrolled diabetes mellitus. Hypernatremia may occur in
dehydration, water deficit, hyperadrenocorticism, and central nervous
system trauma or disease (Bistner, 1995).
Chloride is the major extracellular anion. Chloride and bicarbonate ions
are important in the maintenance of acid-base balance. When chloride in
the form of hydrochloric acid or ammonium chloride is lost, alkalosis
follows; when chloride is retained or ingested, acidosis follows. Elevated
serum chloride levels, hyperchloremia, can be seen in renal disease,
dehydration, overtreatment with saline solution, and carbon dioxide
deficit (as occurs from hyperventilation). Decreased serum chloride
levels, hypochloremia, can be seen in diarrhea and vomiting, renal
disease, overtreatment with certain diuretics, diabetic acidosis,
hypoventilation (as occurs in pneumonia or emphysema), and adrenal
insufficiency (de Morais, 1995).
As seen above, one to two milliliters of blood can give a clinician a great
insight to the way an animals’ systems are functioning. With many more
tests available and being developed every day, diagnosis becomes less
invasive to the patient. The more information that is made available to
the doctor allows a faster diagnosis and recovery for the patient.
Barrie, Joan and Timothy D. G. Watson. ?Hyperlipidemia.?
Current Veterinary Therapy XII. Ed. John Bonagura.
Philadelphia: W. B. Saunders, 1995.
Bistner, Stephen l. Kirk and Bistner’s Handbook of Veterinary
Procedures and Emergency Treatment. Philadelphia: W. B.
de Morais, HSA and William W. Muir. ?Strong Ions and Acid-Base
Disorders.? Current Veterinary Therapy XII. Ed. John
Bonagura. Philadelphia: W. B. Saunders, 1995.
Fraser, Clarence M., ed. The Merck Veterinary Manual, Seventh
Edition. Rahway, N. J.: Merck & Co., 1991.
Garrett, Reginald H. and Charles Grisham. Biochemistry. Fort
Worth: Saunders College Publishing, 1995.
Lehninger, Albert, David Nelson and Michael Cox. Principles of
Biochemistry. New York: Worth Publishers, 1993.
Schmidt-Nielsen, Knut. Animal Physiology: Adaptation and
environment. New York: Cambridge University Press, 1995.
Sodikoff, Charles. Labratory Profiles of Small Animal Diseases.
Santa Barbara: American Veterinary Publications, 1995.